The paper, for which DCRI cardiology fellow Jedrek Wosik, MD, is the corresponding author, details how telehealth has transformed both within the Duke Health system and beyond through the collaboration of people, processes, and technology. The paper focuses on three distinct phases of the crisis caused by the novel coronavirus: outpatient care during the stay-at-home orders, the initial COVID-19 hospital surge, and recovery post-pandemic.

Throughout the stay-at-home orders, the authors write, outpatient care administered via telehealth has increased dramatically. Before the pandemic, telehealth visits accounted for less than 1 percent of visits at Duke; just four weeks later, telehealth visits account for 70 percent of visits with over 1,000 patients seen virtually per day. To streamline this transition, Duke created a centralized telehealth call center and deployed a “train the trainer” model to rapidly onboard over 1,300 providers in three weeks.

Telehealth has also been useful in caring for inpatients during a time when many hospitals have been overloaded. “Telehealth is ideally suited to meet the demands of inpatient care while at the same time reducing virus transmission, stretching human and technical resources, and protecting patients and healthcare workers in the inpatient care setting,” the authors write.

At Duke, specialists have been using a Tele-ICU system that enables them to remotely manage intubated patients. Physicians can see data describing ventilator settings and patient breathing while consulting with the bedside team from a remote location. This approach not only decreases exposure risk, but also conserves personal protective equipment (PPE).

Not much is known about telehealth in the third stage—recovery post-pandemic—because the pandemic is ongoing. However, the authors make recommendations about important areas of focus during this stage. While telehealth was leveraged quickly to respond to a crisis, it will be critical to ensure that data security and patient privacy remain paramount as telehealth becomes a sustained offering integrated into everyday care. This could present an opportunity to leverage the electronic health record, which already provides the infrastructure for patients to securely access test results. Health systems should proactively engage patients, the authors write, while also creating systems that allow for efficient use of hospital space and staff.

The COVID-19 pandemic has ushered in a new era of telemedicine, and “delivery of patient care by the American health system will be forever changed,” the authors write. There is more work ahead to determine how to administer telehealth most efficiently and equitably—for example, by linking rural hospitals to existing telehealth programs from larger hospitals.

June 3, 2020 – The study team used pediatric patients’ electronic health records to identify patients eligible for the study.

A paper recently published in the Pediatric Infectious Disease Journal sheds light on risk factors that make children more likely to contract hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).

HABP/VABP can often be deadly for children, and these illnesses are often caused by drug resistant bacteria that require novel antibiotics. However, HABP/VABP can be difficult to diagnose, which leads to inefficient clinical trial enrollment and hinders new drug development. Identification of risk factors could aid in earlier and more accurate diagnosis of HABP/VABP and improve clinical trials in this area.
The study used pediatric patients’ electronic health records to identify which patients received qualifying respiratory support or antibiotics for either a lower respiratory infection or undifferentiated sepsis. The study then followed the selected patients until they were either diagnosed with HABP/VABP or discharged from the intensive care unit.

“This study, which identifies factors that could place patients at a higher risk of developing hospital-acquired and ventilator-associated bacterial pneumonia, will be important both for diagnosis and prevention purposes,” said the DCRI’s Danny Benjamin, MD, PhD, principal investigator and chair of the PTN.

Of 862 newborns, infants, and children younger than 18 who were evaluated, 10 percent of patients receiving respiratory support and 12 percent overall developed HABP/VABP. While risk factors varied by age group, patients showed increased odds of developing HABP/VABP if they:

Were older

Were shorter

Spent a longer time in the intensive care unit

Were at risk of aspiration

Had received a blood product transfusion in the prior seven days

Had frequent suctioning

“This paper can potentially help improve diagnosis and identification of eligible pediatric participants for antibacterial pneumonia trials,” added Pamela Tenaerts, MD, MBA, executive director of CTTI. “Additional results from CTTI’s HABP/VABP studies project, including the results of this study’s U.S. and European adult cohorts, will be available in the coming months.”

May 28, 2020 – In response to a wide array of cardiovascular complications seen in patients with COVID-19, the Duke Health system has developed a framework which organizes its approach to caring for patients with COVID-19-related myocardial injury, heart failure, arrhythmias, and more.

A recently published paper in American Heart Journal led by DCRI fellow Rahul Loungani, MD (pictured left), under the mentorship of Duke Heart Center Chief and DCRI faculty member Manesh Patel, MD (pictured right), details care pathways established in the Duke Health system for managing patients with cardiovascular complications caused by COVID-19.

“The model presented can provide a framework for other institutions to organize their own approaches and can be adapted to local constraints, resource availability, and emerging knowledge,” the authors write. Additional DCRI authors on the paper include Robert Mentz, MD; Schuyler Jones, MD; Sreekanth Vemulapalli, MD; and Jonathan Piccini, MD, MHS.

Cardiologists have seen a wide range of cardiovascular complications related to the novel coronavirus. Patients with a history of cardiovascular disease who contract COVID-19 are more likely to become critically ill, and potential therapies may also cause complications. The disease has also been known to directly result in complications, including myocardial injury, heart failure, and arrhythmias.

The Duke Division of Cardiology, in partnership with the Duke Heart Center, decided to create a care pathway for patients with COVID-19 to organize its approach to cardiovascular complications and “to streamline care, limit risk to personnel, ensure provision of limited resources (including diagnostics, invasive procedures, and service lines), and align clinical care across multiple divisions.”

The pathway outlines a framework for triaging and caring for patients based on the symptoms that have been seen within each group of complications. Not only is the framework helpful in providing advice for cardiologists, but it also helps provides clear guidance to frontline providers who may not routinely administer cardiovascular care. The model also advises that for high-risk phenotypes, clinicians should consider the opportunity to enroll these patients in clinical trials.

“The pathway we developed is based on expert opinion and the current evidence we have available, and our response will continue to evolve as new evidence emerges,” Loungani said. “In the meantime, we hope that by sharing this pathway, we can help other health systems in shaping their response to the wide-ranging cardiovascular impacts of COVID-19.”

Patel added, “We are all learning about COVID-19 at a rapid pace, and we appreciate the opportunity to share information and update approaches as we all work to help our communities.”

May 26, 2020 – The indication-seeking trial is the first in the SGLT2 inhibitor class to investigate whether empagliflozin can be used to prevent heart failure after a heart attack.

Boehringer Ingelheim and Eli Lilly and Company (NYSE:LLY) today announced an academic research collaboration with the Duke Clinical Research Institute (DCRI) on a new trial, EMPACT-MI (EMPAgliflozin for the prevention of Chronic heart failure and morTality after an acute Myocardial Infarction). The collaboration will investigate whether Jardiance® (empagliflozin) can improve outcomes and prevent heart failure in adults with and without diabetes who have had an acute myocardial infarction, more commonly known as a heart attack. This randomized clinical trial will be conducted, analyzed and reported in partnership with the DCRI, with Boehringer Ingelheim and Lilly providing funding. To conduct the trial, the DCRI will partner closely with the Canadian VIGOUR Centre, an academic research organization committed to the advancement of cardiovascular health.

EMPACT-MI will include approximately 3,300 adults across at least 16 countries who have had an acute myocardial infarction. The primary endpoint of the trial is to assess the effect of Jardiance on all-cause mortality and hospitalization for heart failure. The trial will be part of the EMPOWER program, the broadest and most comprehensive clinical trial program exploring the impact of Jardiance on the lives of people with cardio-renal-metabolic conditions.

“This collaboration represents an important step in understanding how to safeguard and protect the lives of patients with acute myocardial infarction,” said Adrian Hernandez, MD, MHS, co-chair of the EMPACT-MI trial and DCRI executive director. “Myocardial infarction is the leading cause of death in cardiology, and this is the first trial in the SGLT2 inhibitor class to investigate the potential to increase survival and decrease progression to heart failure in people who have had a recent myocardial infarction.”

Javed Butler, MD, MPH, MBA, chair of the EMPACT-MI trial and professor and chairman of the Department of Medicine at the University of Mississippi, added, “We are delighted to lead the EMPACT-MI trial to find out whether Jardiance could become a new standard of care option to improve the outcomes and lives of people with acute myocardial infarction.”

Pragmatic clinical trials focus on the relationship between treatments and outcomes in real-world health system practice. This partnership will leverage the DCRI’s experience in pragmatic trials by implementing innovative and efficient trial elements, including remote follow-up and a focused data collection approach, which enable a strong patient focus while maintaining high data quality.

“We are pleased to collaborate with the Duke Clinical Research Institute on the EMPACT-MI trial to investigate the potential to increase survival and prevent heart failure from developing in adults who have had a heart attack. Despite current therapies, these patients have a high residual risk that could be addressed by the multiple benefits we have observed with SGLT2 inhibition,” said Waheed Jamal, MD, corporate vice president and head of CardioMetabolic Medicine, Boehringer Ingelheim.

“The EMPACT-MI trial is part of our broad and comprehensive clinical development program, which aims to explore how Jardiance can improve health outcomes and fill therapeutic gaps for a broad range of patients suffering from cardio-renal-metabolic conditions,” said Jeff Emmick, MD, PhD, vice president, Product Development, Lilly.

May 18, 2020 – The registry, which has enrolled 1,002 patients with idiopathic pulmonary fibrosis, shares critical knowledge and insights to help combat lung disease.

Clinical researchers at the DCRI continue to uncover new information about idiopathic pulmonary fibrosis (IPF), a devastating, progressive lung disease with an unknown cause, by analyzing data collected through the IPF-PRO/ILD-PRO Registry.

The registry is sponsored by Boehringer Ingelheim (BI) and includes more than 1,000 patients with IPF. The registry’s principal investigator is Scott Palmer, MD, MHS. Other members of the DCRI team include Laurie Snyder, MD, MHS; Jamie Todd, MD; Megan Neely, PhD; Eric Yow, MS; Emily O’Brien, PhD; and Rosalia Blanco, MBA. Work with the registry has been ongoing since 2014 and has, to date, resulted in eight published manuscripts and 40 poster or abstract presentations. Below is a sampling of published findings from the past several months.

“Thanks to the partnership with BI and collaborative efforts of our DCRI team and site investigators over the last six years, we’ve made great progress in improving our understanding of idiopathic pulmonary fibrosis,” Palmer said. “We have been able to rapidly share the knowledge we gain through this registry in order to understand the impact of the disease and its mechanisms and to guide the development of new and improved approaches to patient care and treatment.”

Potential Biomarkers Could Help in Diagnosis, Outcome Predictions

Because timely diagnosis and management of IPF are both challenges, much of Todd’s research focuses on determining whether there are biomarkers that could help clinicians in diagnosis, prognosis, or predicting how patients will respond to treatment. In addition, these highly translational studies are providing new and fundamental insights into IPF disease mechanisms by leveraging the unique biosamples prospectively collected among patients enrolled in the registry.

A recent study led by Todd and published in BioMed Central Pulmonary Medicine compared blood samples of patients enrolled in the IPF-PRO Registry with the blood of patients without lung disease. The study, which quantified the expression of a broad array of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), shed light on how the expression of single MMPs and TIMPs relates to status and severity of IPF. However, because almost all of the MMPs and TIMPs presented in elevated levels in patients with IPF, the study also sought to show how combinations of MMPs and TIMPs aid in diagnosis or prognosis in patients with IPF. Although further validation of the study’s results will be necessary, Todd said, this study is a step toward identifying biomarkers that could be useful in future diagnosis and treatment of IPF.

Other DCRI contributors to this study include Palmer, Neely, and Robert Overton. Duke’s L. Kristin Newby, MD, is principal investigator of the MURDOCK study, which provided the control group for this study and contributed to the publication.

Proteins in Plasma Found to be Associated with Death, Lung Transplant

Another study led by Todd found that, when considered along with clinical factors such as forced vital capacity and diffusion capacity, 65 proteins were significantly associated with the composite outcome of death or lung transplant. When proteins were considered without clinical factors, a set of 55 proteins could be used to predict the probability of respiratory death or lung transplant.

The study examined proteins in the plasma of 300 IPF-PRO Registry participants who had cases diagnosed or confirmed within a six-month timeframe. An abstract detailing the study was accepted at American Thoracic Society’s annual conference (ATS 2020) and was published in the ATS abstract edition of the American Journal of Respiratory and Critical Care Medicine online after the conference was canceled due to COVID-19. Neely and Palmer also contributed to this study, and Overton and Hillary Mulder, MS, provided statistical support.

Insights on Time to Diagnose IPF

A study led by Snyder studied a cohort of IPF-PRO participants to determine how long it took for patients to receive an IPF diagnosis after the first symptom onset or imaging evidence of pulmonary fibrosis. The study also compared the time from enrollment in the registry to death or lung transplant between the two groups of patients. An abstract detailing the study accepted at ATS 2020 and was published in the ATS abstract edition of the American Journal of Respiratory and Critical Care Medicine online. Neely, Hellkamp, and DCRI fellow Christopher Mosher, MD, also contributed to this study.

Measures of IPF Severity Correspond to Patient-Reported Quality of Life

A study led by O’Brien and published in Chest examined the associations between objective disease severity measures collected as part of the IPF-PRO Registry—such as diffusing capacity for carbon monoxide, oxygen use at risk and with activity, and an index score determined by age, gender, and lung function—and patient-reported quality of life measures based on a questionnaire.

The study found that quality of life was worse in patients enrolled in IPF-PRO compared with the general population. Increasing disease severity was also associated with worse quality of life. Other DCRI contributors include Snyder; Todd; Palmer; Neely; Aparna Swaminathan, MD; and Anne Hellkamp, MS.

Expanding on the IPF-PRO Registry Model

A related group of respiratory illness that needs further investigation is the broader category of interstitial lung disease (ILD) other than IPF, as it is now clear a subset of these patients develop a relentless and progressive fibrosis similar to patients with IPF.

Building on the success of the IPF-PRO Registry, the DCRI, again in partnership with BI, expanded the registry to include patients with ILD who demonstrate evidence of progressive fibrosis. The ILD-PRO Registry, which will also be led by Palmer and the same leadership from the DCRI team, will enroll approximately 1,000 patients with ILDs across 45 sites nationwide, drawing on the infrastructure already established by the IPF-PRO Registry. An abstract detailing the design of the ILD-PRO Registry was accepted at ATS 2020 and was also published in the ATS abstract edition of American Journal of Respiratory and Critical Care Medicine online.

Neely, Snyder, O’Brien, and Todd also contributed to this abstract and will serve as co-investigators on the ILD-PRO Registry. Todd is the biomarker committee co-chair and Snyder is the publication committee co-chair for all of the registry studies.

May 13, 2020 – Data provided to the FDA by the research network has helped to provide a fuller picture for prescribing these medications to pediatric populations.

Data from the Pediatric Trials Network (PTN) recently contributed to label changes for three different drugs, the culmination of months of research pursued by the NIH-supported research network.

Label changes occur when the U.S. FDA updates the prescribing information for a drug. In all three of these cases, the FDA added prescribing information to be used when treating children. The PTN, for which the DCRI serves as a coordinating center, is focused on conducting trials to improve drug labeling for children.

The three drugs that can now be used safely and effectively when treating children are:

Clindamycin. The label now includes dosing guidelines for children with obesity. While Clindamycin is a commonly used pediatric drug, it is important to consider dosing for children with obesity separately because their bodies may absorb and process drugs differently.

Caffeine citrate. The label now includes crucial information about age and dosing. Caffeine citrate is the most commonly used non-antimicrobial medication for premature infants used in the newborn intensive care unit. When given to premature infants, caffeine reduces episodes of apnea (forgetting to breathe) and bradycardia (slowing of the heart rate) that can result from an immature nervous system.

Doxycycline. This drug has never been well studied in children younger than 8, but thanks to data from a PTN study called PTN POPS, the label now contains better information on how to use this drug in treating young children. Doxycycline is an antibiotic used to treat diseases such as Rocky Mountain Spotted Fever and methicillin resistant staph aureus.

To date, the PTN has contributed to label changes for 15 drugs.

“With each label change, the PTN is giving pediatricians more of the critical information they need to improve the lives of their patients and give parents more confidence in their children’s care,” said the DCRI’s Kanecia Zimmerman, MD, MPH, associate professor of pediatrics at Duke University School of Medicine and chair of the PTN steering committee.

“These label changes reflect the flexible and creative approach that everyone working with the PTN has collectively advanced,” said Danny Benjamin, MD, PhD, principal investigator for the PTN and director of DCRI Pediatrics. “The network is well-positioned for the next several years to continue to improve the health of children, thanks to legislation that supports pediatric research and the quality of our work.”

May 8, 2020 – A pragmatic comparative effectiveness study comparing Micra leadless pacemakers to conventional transvenous pacemakers found that for patients who received the novel leadless pacemakers, complication risks were reduced by two-thirds six months post-procedure.

Results from the Novel Micra Continued Evidence Development (Micra CED) post-approval study confirm the safety and efficacy of a novel tined leadless pacemaker and reveal promising insights about how this novel device can improve patient outcomes.

Results from the study, which were presented virtually as a late-breaking session at the Heart Rhythm Society 2020 Science program, showed that patients who were treated with the Micra Transcatheter Pacing System, a novel tined leadless pacemaker developed by Medtronic, had a lower rate of complications in follow-up compared to those patients who received a conventional transvenous pacemaker.

One in eight patients may experience a complication with the traditional pacemakers, explained the DCRI’s Jonathan Piccini, MD, MHS, who led the study and gave the presentation. Leadless pacemakers eliminate the complications associated with pacemaker pockets and transvenous leads.

The Micra IDE study, a pivotal study conducted between 2013 and 2017 to assess the safety and efficacy of Micra, found a 48 percent reduction in complication risk when compared to historical studies of transvenous pacemakers. A key question was whether these same benefits would be identified or generalizable in routine clinical practice. The Micra CED pragmatic comparative effectiveness study sought to compare not only complications for patients at 30 days and at 6 months, but also the rate at which patients experienced a need for pacemaker system revision or all-cause mortality. Micra CED identified a 63 percent lower risk of complications in follow-up at 6 months.

Micra CED utilized a unique pragmatic design that focused on patients 65 years of age and older who received a de novo pacemaker within the Medicare program. In the nationwide cohort, 5,700 patients who received a Micra leadless pacemaker were compared to 9,600 patients who received a transvenous pacemaker. Because the investigators were interested in determining whether results from prior Micra studies, including the IDE trial, were generalizable to a wider population, they paid special attention to characteristics of the patient populations in each study. Patients in Micra CED had higher rates of comorbid illness, including a nearly three-fold higher prevalence of heart failure and a greater than two-fold higher prevalence of COPD when compared to the pivotal Micra IDE trial.

The Micra CED study team found no significant difference in overall complications between the two groups of patients 30 days after receiving the device. The group that received Micra had lower rates of device-related complications, but higher rates of complications related to the access site and higher rates of cardiac effusions/perforation. However, the latter event rate was less than 1 percent in both groups.

Patients who received Micra saw greater benefit six months after receiving the device, when their risk of complications was reduced by two-thirds as compared to patients who received transvenous pacemakers. This association with lower complication rates in follow-up is especially significant because the group of patients who received Micra tended to be sicker and had more comorbid illnesses than prior Micra studies.

The study team found no significant difference in the study’s other two objectives: rate of system revision and all-cause mortality.

“These results show promise for the many patients who rely on permanent pacing as an essential therapy,” Piccini said. “The Micra CED study reinforces what we have seen in prior studies. Patients who received Micra leadless pacemakers experienced improved outcomes over the long term, including lower rates of complications at six months. Not only does this study illustrate the feasibility of utilizing real-world data to generate evidence and measure the effectiveness of new technology, but it provides needed information that will help clinicians in shared decision-making with their patients.”

May 6, 2020 – A cardiologist and internationally recognized clinical research expert will become the Institute’s new leader.

After a nationwide search for a new leader for the Duke Clinical Research Institute, the Duke University School of Medicine announced today it has named an executive director for the Institute.

Adrian Hernandez, MD, MHS, a cardiologist and internationally recognized clinical research expert, will step into the role effective May 15. Hernandez, who has served as the Vice Dean for Clinical Research for the Duke University School of Medicine since 2017, will also maintain some responsibilities of this role as he continues to guide clinical research strategy for the School.

Hernandez has a long history with the DCRI, having joined as a cardiology fellow in 2002. “I learned the power of evidence, the importance of teams, and about the unmet needs of people with everyday health challenges,” Hernandez said while reflecting on the beginnings of his DCRI career. “This early experience continues to shape my vision and thinking today. Simply put, it’s great to be back home.”

Hernandez outlined parts of his vision for the DCRI’s future in creating and implementing new models for conducting clinical research. “Our value will be realized through more efficient studies and in creating new pathways for innovative health solutions and groundbreaking research,” he said. “The future of our work will emphasize programs that are large, leveraged, and embedded within health systems or the daily lives of people. We will practice new methods that enable research at home that is frictionless, flexible, and even fun. To accomplish this, we will continue to leverage the many strengths across Duke and the School of Medicine to innovate locally and scale globally.”

Lesley Curtis, PhD, will transition out of her Interim Executive Director role and resume her full-time work as Chair and Professor of Duke’s Department of Population Health Sciences. She will also remain an active DCRI faculty member through her leadership of the DCRI Think Tanks program and her work with the NIH Collaboratory, PCORnet, and other joint research projects between the DCRI and Population Health.

“Leading the DCRI has been a rewarding journey in so many ways, and together we have made terrific progress,” Curtis said. “I remain committed to the DCRI mission and its ongoing success. I am also delighted to hand over the reins to someone who is a leading clinical researcher, a close colleague, and a substantial contributor to the DCRI for many years.”

April 29, 2020 – In response to the COVID-19 pandemic, the POP02 study has expanded its protocol to include antiviral drugs that could be used to treat pediatric patients with COVID-19.

The Pediatric Trials Network (PTN) is expanding one of its existing studies to focus on pediatric dosing for six antiviral drugs that may be used in the treatment of COVID-19.

In a matter of weeks, Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POP02), was able to expand its protocol to focus on potential COVID-19 therapies and begin enrolling pediatric patients who are already taking these medications per standard of care. POP02 will collect data on azithromycin, chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, and tocilizumab. The study, which will be led by Duke’s Chi Hornik, PharmD, Director of Clinical Research in the Division of Pediatric Critical Care Medicine, will include about 30 sites. Researchers aim to enroll 36 patients taking each drug.

The PTN, for which the DCRI serves as a coordinating center, is a research network focused on determining safe and effective drug dosing standards for children.

POP02 is an extension of another PTN study, PTN POPS. The aim of both studies is to leverage procedures conducted during routine patient care, such as blood draws, and use pharmacokinetic modeling to determine safe and effective dosing information for different pediatric age groups and special pediatric populations.

“PTN serves as a national collaborative resource, providing evidence for optimal dosing of commonly used medications in infants and children,” said Danny Benjamin, MD, PhD, MPH, principal investigator and chair of the PTN. “Our expanded POP02 work will be instrumental in helping inform the decisions parents and healthcare providers make when caring for our youngest patients with COVID-19.”

April 22, 2020 – A paper authored by the DCRI’s Adrian Hernandez, MD, MHS, and colleagues calls for major changes in the research ecosystem to enable pragmatic trials, especially those comparing different treatments in order to generate evidence needed to guide decisions in clinical practice.

Reducing uncertainty in clinical practice will require a move toward a learning health system in which research is embedded in clinical care, write the authors of a recent Perspective piece published in the New England Journal of Medicine.

The DCRI’s Adrian Hernandez, MD, MHS, Professor of Medicine and Vice Dean for Clinical Research for the Duke University School of Medicine, was one of the authors for this publication, which comments on a goal set in 2010 by the National Academy of Medicine (NAM). The goal outlined that by 2020, “90 percent of clinical decisions will be supported by accurate, timely, and up-to-date clinical information, and will reflect the best available evidence.” The paper’s authors argue that uncertainty still abounds in clinical practice, with little or no evidence in many cases and “haphazard, arbitrary selection” guiding treatment decisions.

While data from observational studies and health records can fill some of these gaps, randomization “remains the best tool for the unbiased comparison of many alternative treatments,” the authors write. However, traditional randomized clinical trials are slow to provide much-needed evidence, and because of highly specific inclusion criteria, results are often not generalizable to a wider population.

To address this problem, the authors recommend major changes in the ecosystem to enable clinical trials that are embedded into clinical practice and address common decisional dilemmas for clinicians. The majority of current pragmatic trials compare current clinical practice to proposed improvements rather than comparing two or more treatments to determine which results in better outcomes. The NIH Health Care Systems Research Collaboratory and PCORnet®, the National Patient-Centered Clinical Research Network, are two entities that work on pragmatic clinical trials, and the DCRI serves as a coordinating center for both entities. The paper’s authors draw on their experience working with both organizations to identify the challenges of conducting pragmatic trials especially designed to study head-to-head comparisons. The authors’ observations include:

There is a false impression of certainty in clinical practice, and more transparency is needed around uncertainty.

Meaningful engagement with stakeholders is necessary, as research “should focus on questions and outcomes that are important to patients, clinicians, and health care systems.”

Health systems that have established infrastructure and the resources needed to conduct pragmatic trials and implement a learning health system are more likely to be successful.

Navigating these challenges will require buy-in from many stakeholders, including:

Health system leaders must place value on rigorous evidence generation and consider it “a core function of ordinary health care.”

Research sponsors must support infrastructure for embedded research and fund projects that answer questions that can make an impact on population health.

Regulators must consider aligning consent procedures with research risk, as randomization is no more risky than the guesswork that occurs in today’s uncertain clinical practice environment.

Researchers must ask real-world questions that are important to patients, caregivers, and clinicians.

Although the NAM’s goal for evidence-based decisions remains distant, the authors write, progress will only begin when all of these parties recognize that the current evidence is not sufficient and come together to institute change.

Other authors of the paper include Gregory Simon, MD, MPH, of the Kaiser Permanente Washington Health Research Institute and Richard Platt, MD, MSc, of the Harvard Pilgrim Health Care Institute. Both of these institutes serve as part of the NIH Collaboratory coordinating center along with the DCRI.

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